There are currently recognized to be 27 human papillomaviruses and 6 bovine papilomaviruses. Each of these viruses is associated with distinct clinical entities which in humans include common warts, condyloma accuminata, laryngeal papillomatosis, and the macular pityriasis-like lesions of epidermodysplasia verruciformis. In cattle, these lesions are associated with cutaneous fibropapillomas and esophageal papillomatosis among other lesions. To date, no tissue culture system has been developed to propagate the papillomaviruses. There is a subset of papillomaviruses which are associated with cancers in their natural hosts. Among the human papillomaviruses, these include HPV-5 and HPV-8 in patients with epidermodysplasia verruciformis, and HPV-16 and HPV-18 in human cervical carcinomas. In cattle, it includes BPV-4 in cattle which feed on bracken fern. In the laboratory, we have focused our attention on the molecular biology of BPV-1, because it is capable of transforming susceptible rodent cells in culture. Transformation of rodent fibroblasts by papillomviruses thus remains one of the only biological systems available to the study of the papillomaviruses. A unique feature of this papillomavirus transformation system is that the viral DNA does not integrate into the host chromosome necessarily upon transformation. The DNA may remain extra-chromosomal as a stable multicopy plasmid. The factors involved in stable transformation as well as stable plasmid maintenance, are being extensively studied. A second feature associated with papillomavirus infection is the propensity of certain lesions caused by certain viruses to progress to carcinomas. What factors are involved in the progression of a benign lesion to a carcinoma, are not known. Studies involving the Shope papillomavirus and Shope papillomavirus-induced carcinomas are underway to define whether activated oncogenes in addition to the viral sequences may be associated with this progression.